The biosynthesis of fatty acids is carried out by an acetyl CoA carboxylase and a fatty acid synthase. LCE is one of the fatty acid synthases, and it is known that in a fatty acid synthesis pathway in which the synthesis is started using acetyl CoA as a substrate, LCE elongates a carbon chain of mainly a fatty acid having 12 or more carbon atoms, for example, lauric acid to myristic acid, myristic acid to palmitic acid, palmitic acid to stearic acid, palmitoleic acid to vaccenic acid, and so on [J. Biol. Chem., 276 (48), 45358-45366, (2001)] (Non-patent document 1). Further, it is known that excess long-chain fatty acids in the body cause an increase in neutral fat, phospholipid, cholesteryl ester, and the like, and moreover causes accumulation of fat.
Further, it is known that excessively accumulated fat causes, for example, insulin resistance, diabetes, hypertension, hyperlipidemia, obesity and the like, and when several these factors are combined, risk of onset of atherosclerosis is significantly increased, and such symptoms are called metabolic syndrome. It is also known that high neutral fat or obesity increases risk of, for example, pancreatitis, hepatic dysfunction, cancer such as breast cancer, uterine cancer, ovarian cancer, colon cancer or prostate cancer, menstrual abnormality, arthritis, gout, cholecystitis, gastroesophageal reflux, obesity hypoventilation syndrome (Pickwickian syndrome), sleep apnea syndrome and the like. It is widely known that diabetes often leads to, onset of, for example, angina pectoris, heart failure, stroke, claudication, retinopathy, failing vision, renal failure, neuropathy, skin ulcer, infection and so on [see The Merck Manual of Medical Information], second home edition, Merck & Co., 2003].
Accordingly, an LCE inhibitor is useful as a preventive and/or remedy for these diseases.
As conventionally known benzoxazinone derivatives, for example, those described in JP-T-2002-543193 can be exemplified. These compounds have a benzoxazinone backbone, however, the R2 moiety in the present invention is limited to C1-6 alkyl or C2-6 alkenyl, and therefore, they are different from those of the present invention. Further, this reference example relates to a progesterone receptor modulator, and there is no disclosure of an LCE inhibitory effect.
Further, compounds having an LCE inhibitory activity have been completely unknown until now.    Non-patent document 1: J. Biol. Chem., 276 (48), 45358-45366, (2001)    Patent document 1: JP-T-2002-543193